Abstract
Comparative pharmacokinetic and pharmacodynamic studies on erythropoietin administered alone or in combination with sodium hyaluronate were performed in rats to demonstrate the potential application of sodium hyaluronate to a sustained release formulation of erythropoietin (SRE). Following subcutaneonus administration, serum erythropoietin levels in the rats treated with SRE persisted longer than those in the rats treated with an erythropoietin solution. Administration of a bulk erythropoietin solution once a week yielded a remarkable effect on erythropoiesis. The time-course profiles of hematocrit and hemoglobin level, however, were rather fluctuating, indicating that adverse effects, such as hypertension, might be incurred. In contrast, weekly administration of SRE comprising sodium hyaluronate, erythropoietin, and serum albumin gave smoother time-course profiles of erythropoiesis. Serum albumin was found to play an important role in SRE. Since preparation of SRE requires neither organic solvent nor heating, possibility of losing biological activity of erythropoietin would be minizized. The viscous property of SRE would lead to the stabilization of erythropoietin against physical disturbance, which would be beneficial especially for self-administration dosage form. In addition, the fluidity of SRE allowed subcutaneous injection with a small gauge needle (e. g., 26 G). Considering that sodium hyaluronate is biocompatible and biodegradable, the SRE proposed in this study would be a promising candidate for weekly formulation of erythropoietin.
